The Study of Signal Pathway Regulating the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

ZHOU Chen-chen, WU Zu-ping, ZOU Shu-juan

Abstract

Osteogenesis of mesenchymal stem cells to differentiate between bone marrow by multiple signaling pathways that control, directly or indirectly affect small related transcription factor 2 (runt-related transcription factor 2, Runx2) and osteoblast specific transcription factor (osterix, Osx), the expression of osteogenesis key transcription factors, such as in the development and regeneration of the bone, bone repair has played a key role in the process of reconstruction. These pathways play their mechanism of action, but also intertwined associated constitute a complex signal transduction network, but due to the limitations of research methods, the osteogenic differentiation related signaling pathways of the specific mechanism is still unclear, if you can clarify these different signaling pathways play to the role of their relevant mechanism and the relationship between various pathways and the mechanism study of osteogenesis differentiation is of great importance. This article will review the progress of various signaling pathways in the regulation of osteogenic differentiation of bone marrow mesenchymal stem cells.

 

Keywords: Bone mesenchymal stem cells, Osteogenic differentiation, Signaling pathway

 

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References


PITTENGER M， MACKAY A， BECK S， et al. Multilineage potential of adult human mensenchymal stem cells. Science，1999，284: 143–147.

CHAMBERLAIN J R， SCHWARZE U， WANG P R， et al. Gene targeting in stem cells from individuals with osteogenesis imperfect. Science，2004，303(5661): 1198–1201.

KANG M I， LEE W Y， OH K W， et al. The short-term changes of bone mineral metabolism following bone marrow transplantation. Bone，2000， 26(3): 275–279.

PINSON K I， BRENNAN J， MONKLEY S， et al. An LDL-receptorrelated protein mediates Wnt signalling in mice. Nature，2000， 407(769): 535–538.

DAVIDSON G， WU W， SHEN J， et al. Casein kinase 1 γcouples Wnt receptoractivation to cytoplasmic signal transduction. Nature，2005， 438(7069): 867–872.

FIDDES I T， LODEWIJK G A， MEGHAN M， et al. Human-specific NOTCH2NL genes affect notch signaling and cortical neurogenesis. Cell， 2018， 173(6): 1356–1369.e22[2020-06-08]. https://doi.org/10.1016/j.cell.2018.03.051.

PETER S M， SUSAN W. A review of Notch processing with new insights into ligand-independent Notch signaling in T-cells. Front Immunol， 2018， 9: 1230[2020-06-08]. https://doi.org/10.3389/fimmu.2018.01230.

CARBALLO G B， HONORATO J R， DE LOPES G P F， et al. A highlight on sonic Hedgehog pathway. Cell Commun Signal， 2018， 16(1): 11[2020-06-08]. https://biosignaling.biomedcentral.com/articles/10.1186/s12964-018-0220-7. doi: 10.1186/s12964-018-0220-7.

PETROV K， WIERBOWSKI B M， SALIC A. Sending and receiving Hedgehog signals. Annu Rev Cell Dev Biol，2017，33(1): 145–168.

YAMASHIRO T， ZHENG L， SHITAKU Y， et al. Wnt10a regulates dentin sialophosphoprotein mRNA expression and possibly links odontoblast differentiation and tooth morphogenesis. Differentiation， 2007，75(5): 452–462.

YANG J， WANG S K， CHOI M， et al. Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Mol Genet Genomic Med，2015，3(1): 40–58.

SASAKI K， HITORA T， NAKAMURA O， et al. The role of MAPK pathway in bone and soft tissue tumors. Anticancer Res，2011，31(2): 549–553.

BONNI A， BRUNET A， WEST A E， et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science，1999，286(5443): 1358–1362.

ITOH N， ORNITZ D M. Evolution of the FGF and FGFR gene families. Trends Genet，2004，20(11): 563–569.

ORNITZ D M， MARIE P J. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev，2002，16(12): 1446–1465.

WOODS A， WANG G， BEIER F. RhoA/ROCK signaling regulates Sox9 expression and actin organization during chondrogenesis. J Biol Chem， 2005，280(12): 11626–11634.

MCBEATH R， PIRONE D M， NELSON C M， et al. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell，2004，6(4): 483–495.

ONGARO A， PELLATI A， BAGHERI L， et al. Characterization of Notch signaling during osteogenic differentiation in human osteosarcoma Cell Line MG63. J Cell Physiol，2016，231(12): 2652–2663.

CAO J， WEI Y， LIAN J， et al. Notch signaling pathway promotes osteogenic differentiation of mesenchymal stem cells by enhancing BMP9/Smad signaling. Int J Mol Med，2017，40(2): 378–388.

JI Y， KE Y， GAO S. Intermittent activation of notch signaling promotes bone formation. Am J Transl Res，2017，9(6): 2933–2944.

TEZUKA K I， YASUDA M， WATANABE N， et al. Stimulation of osteoblastic cell differentiation by Notch. J Bone Miner Res，2002，17(2): 231–239.

DEREGOWSKI V， GAZZERRO E， PRIEST L， et al. Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/β-Catenin but not bone morphogenetic protein signaling. J Biol Chem，2006， 281(10): 6203–6210.

WENG A P， FERRANDO A A， LEE W， et al. Activating mutations of Notch1 in human T cell acute lymphoblastic leukemia. Science，2004， 306(5694): 269–271.

CUADRADO A， NEBREDA A R. Mechanisms and functions of p38 MAPK signalling. Biochem J，2010，429(3): 403–417.

BIANCHI E N， FERRARI S L. Beta-arrestin2 regulates para-thyroid hormone effects on a p38 MAPK and NFkappaB gene expression network in osteoblasts. Bone，2009，45(4): 716–725.

NOTH U， TULI R， SEGHATOLESLAMI R， et al. Activationof p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts. Exp Cell Res，2003，291(1): 201–211.

NÜSSLEIN-VOLHARD C， WIESCHAUS E. Mutations affecting segment number and polarity in drosophila. Nature，1980，287(5785): 795–801.

TIDYMAN W E， RAUEN K A. The RASopathies: developmental syndromes of Ras/MAPK pathway dysregulation. Curr Opin Gene Dev， 2009，19(3): 230–236.

PENGJAM Y， MADHYASTHA H， MADHYASTHA R， et al. Anthraquinone glycoside aloin induces osteogenic initiation of MC3T3-E1 cells: involvement of MAPK mediated Wnt and Bmp signaling. Biomol Ther (Seoul)，2016，24(2): 123–131.

HUANG Y F， LIN J J， LIN C H， et al. c-Jun N-terminal kinase 1 negatively regulates osteoblastic differentiation induced by BMP2 via phosphorylation of Runx2 at Ser104. J Bone Mine Res，2012，27(5): 1093–1105.

MATSUSHITA T， CHAN Y Y， KAWANAMI A， et al. Extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in osteoblast differentiation and in supporting osteoclastogenesis. Mol Cell Biol，2009，29(21): 5843–5857.

XIAO G， JIANG D， THOMAS P， et al. MAPK pathwaysactivate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem，2000，275(6): 4453–4459.

LIU L S， LU J Q， LI X L. The LIS1/NDE1 complex is essential for FGF signaling by regulating FGF receptor intracellular trafficking. Cell Rep， 2018，22(12): 3277–3291.

MARUYAMA T， MIRANDO A J， DENG C X， et al. The balance of WNT and FGF signaling influences mesenchymal stem cell fateduring skeletal development. Sci Signal， 2010， 3(123): ra40[2020-06-08]. https://stke.sciencemag.org/content/3/123/ra40.long. doi: 10.1126/scisignal.2000727.

WU M， CHEN G， LI Y P. TGF-β and BMP signaling inosteoblast， keletal development， and bone formation， homeostasis and disease. Bone Res， 2016， 4: 16009[2020-06-08]. https://www.nature.com/articles/boneres20169. doi: 10.1038/boneres.2016.9.

JIANG T， GE S， SHIM Y H， et al. Bone morphogenetic protein is required for fibroblast growth factor 2-dependent later-stage osteoblastic differentiation in cranial suture cells. Int J Clin Exp Pathol，2015，8(3): 2946–2954.


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